NORD gratefully acknowledges Marco Castori, MD, Clinical Geneticist, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy, for assistance in the preparation of this report.
VACTERL association is a rare disorder affecting multiple organ systems. Affected children have multiple problems apparent at birth (congenital birth defects) and some of them could be observed on prenatal ultrasound. A few characteristics of VACTERL association do not develop or are not apparent until later during life. VACTERL association is a diagnosis of exclusion (see Related Disorders) and no set of validated diagnostic criteria has been published to date. At the moment, the most stringent approach defines a “secure” designation of VACTERL association in presence of at least one anomaly in all three involved body parts (i.e. limbs, thorax and pelvis/lower abdomen), and “probable” in presence of two or more anomalies in two body parts. CGH-array at standard resolution and exclusion of Fanconi anemia (see below) by DEB test are easily accessible tests which may support the diagnosis. The specific symptoms present will vary greatly from one child to another. Affected children will not have all of the symptoms listed below.
Vertebral abnormalities are defects of the spinal column. Children with VACTERL association may have malformed vertebrae (missing vertebrae, hemivertebrae, “butterfly” vertebrae, vertebral clefts and fusions) and ribs (absent ribs, supernumerary ribs, rib fusions and splitting). In some cases, abnormal side-to-side curvature of the spine (scoliosis) and absence of the tailbone, the lowest bone of the spinal column (sacral agenesis) may also occur.
Some children with VACTERL association may have a condition in which a thin covering blocks the anal opening or the passage that normally connects the anus and the lowest part of the large intestine (rectum) fails to develop, a condition is known as anal atresia or imperforate anus. This condition prevents the normal passage of bowel contents. Some studies suggest that the involvement of the rectum/anus relates to a major risk for genital anomalies, which are usually more serious in boys.
The most common heart defect in children with VACTERL association is ventricular septal defects (VSDs). The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, the main vessel of arterial circulation, carries blood away from the left ventricle to the rest of the body. A VSD may occur in any portion of the ventricular septum. The size and location of the defect determine the severity of the symptoms. A small ventricular septal defect may close on its own (spontaneously) or become less significant as the child matures and grows. A moderately-sized defect may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive heart failure). Symptoms associated with heart failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), failure to grow at the expected rate (failure to thrive), and/or other findings. A large ventricular septal defect may cause life-threatening complications during infancy.
Additional congenital heart defects associated with the disorder may include atrial septal defects (ASDs); hypoplastic left heart syndrome, a life-treating condition in which there is underdevelopment of the left ventricle, the aortic and/or mitral valve, and the ascending aorta; patent ductus arteriosus, a condition in which the passage (ductus) between the blood vessel that leads to the lungs (pulmonary artery) and the major artery of the body (aorta) fails to close after birth; transposition of the great arteries, a condition in which the aortic and pulmonary arteries are in one another’s normal positions; and a condition known as tetralogy of Fallot. (For more information on this disorder, choose tetralogy of Fallot as your search term in the Rare Disease Database.)
Tracheoesophageal Fistula and/or Esophageal Atresia
Children with VACTERL association often have an abnormal connection between the windpipe and the tube that carries food from the throat to the stomach (tracheoesophageal fistula) potentially causing food to be inhaled (aspirated) into the lungs, which, in turn, may result in respiratory infections (e.g., pneumonia) and failure to thrive. In addition, esophageal atresia may be present. Esophageal atresia is a condition in which the tube (esophagus) that normally carries food from the mouth to the stomach narrows to a thin cord or ends in a pouch rather than providing passage to the stomach. These two conditions may result in feeding and swallowing difficulties.
Children with VACTERL association often have a variety of abnormalities affecting the kidneys and urinary tract including lack of development of one or both kidneys (renal aplasia), malformation of one or both kidneys (renal dysplasia), displaced or malpositioned kidneys (renal ectopia), abnormal backflow (reflux) of urine into the tube (ureter) that carries urine to the bladder (vesicoureteral reflux), resulting in abnormal accumulation of urine in the kidneys (hydronephrosis). In addition, affected children may experience frequent urinary tract infections and the urethral opening may not be at the end of the penis (hypospadias).
Another major finding associated with VACTERL association are defects affecting the lower arm bone on the thumb side (radius). These defects may include failure of the radius to grow (radial aplasia), underdevelopment of the radius (radial hypoplasia), underdevelopment or absence of the thumb and/or the presence of an extra bone in the thumb (triphalangealtumb). In addition, affected children may have other limb anomalies including extra digits (polydactyly), webbing of the digits (syndactyly), abnormal fusion of the two forearm bones (radiaoulnarsynostosis) and lower limb malformations (such as clubfoot, and hypoplasia of the great toe and tibia).
Some infants with VACTERL association may experience growth deficiencies and failure to thrive. In some cases, a single umbilical artery instead of the normal two may be present. In most cases of VACTERL association mental functioning and intelligence are unaffected.
Additional abnormalities that have been reported to occur in some individuals with VACTERL association include mild facial asymmetry (hemifacialmicrosomia), ear anomalies, narrowing of the voice box (laryngeal stenosis), narrowing of the passages from the back of the nose to the throat that make it possible to breathe through the nose (choanal atresia), incomplete lobation of the lungs, protrusion of part of the intestines through an abnormal opening in the muscular abdominal wall near the umbilical cord (omphalocele), intestinal malrotation, and a condition called tethered spinal cord syndrome. (For information on this condition, choose tethered spinal cord as your search term in the Rare Disease Database.)
The exact cause of VACTERL association is unknown. No specific genetic or environmental cause has been identified. The vast majority of cases of VACTERL association occur randomly, for no apparent reason (sporadically). In rare cases, VACTERL association has occurred in more than one family member.
Some researchers believe that abnormalities occurring in VACTERL association may result from defects in the middle (mesodermal) layer of the primary layers of the embryo during fetal development due to a variety of reasons. More specifically, VACTERL association results from an insult, heterogeneous in nature, which affects the embryo in the early prenatal life (blastogenesis; i.e. first two-four weeks of gestation).
One or more VACTERL features have occurred with greater frequency to women with diabetes than in the general population. A very few cases of VACTERL association have been associated with mutations in FGF8 and mitochondrial DNA.
Multiple VACTERL features could be also observed in chromosomal disorders, such as trisomy 18 syndrome or Fanconi anemia.
One estimate places the incidence of VACTERL association at 1.6 per 10,000 live births. The true frequency of may be difficult to determine because many cases may be misdiagnosed or undiagnosed, especially children with fewer problems. Although many features of VACTERL association are apparent at birth, some features will not be apparent for weeks, months, or perhaps years. The recurrence risk of VACTERL association for parents with one affected child is about two-three percent. No specific test in actually available for prenatal diagnosis, although fetal ultrasound scan may be of some help to exclude recurrence.
Because the cause of VACTERL association is unknown, no laboratory test exists that can diagnose or rule out VACTERL association. The diagnosis is a clinical diagnosis based on the features seen. It may take some time to do all the testing necessary to make a diagnosis of VACTERL association. A diagnosis may be made based upon a complete physical exam and a variety of specialized tests that look for the major and minor features of VACTERL association listed above.
Although children with VACTERL association have many problems, they can survive and become healthy, happy citizens. The treatment of VACTERL association is directed toward the specific symptoms that are apparent in each individual, which often varies greatly. Many of the structural abnormalities (radial defects, heart defects, anal atresia, etc.) can be surgically corrected.
Infants diagnosed with VACTERL association will need to be followed by a number of medical and developmental specialists depending on their individual needs. Some of the medical specialists who often follow children with VACTERL association include cardiologists, urologists, orthopedists, and ear, nose and throat physicians and clinical geneticists.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. A team approach is essential for these complex children.
The Vertical Expandable Prosthetic Titanium Rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. The titanium rib was developed at the University of Texas Health Science Center in San Antonio. It is manufactured by Synthes Spine Co.: http://www.synthes.com/sites/NA/Products/Spine/Screw_Hook_Rod_and_Clamp_System/Pages/VEPTR_and_VEPTR_II.aspx
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Contact for additional information about VACTERL association:
Marco Castori, MD, PhD
San Camillo-Forlanini Hospital
I-00152 Rome, Italy
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